{"doi":"10.1101/2023.09.16.558069","title":"Poly-basic peptides and polymers as new drug candidate against <i>Plasmodium falciparum</i>","abstract":"Abstract Plasmodium falciparum , the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs like lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite’s growing resistance to existing therapies. Our study shows that a common characteristic of the P. falciparum proteome – stretches of poly-lysine residues such as those found in proteins related to adhesion and pathogenicity – can serve as an effective peptide treatment for infected erythrocytes. A single dose of these poly-basic peptides can successfully diminish parasitemia in human erythrocytes in vitro with minimal toxicity. The effectiveness of the treatment correlates with the length of the poly-lysine peptide, with 30 lysine peptides supporting the eradication of erythrocytic parasites within 72 hours. PEG-ylation of the poly-lysine peptides or utilizing poly-lysine dendrimers and polymers further increases parasite clearance efficiency and bolsters the stability of these potential new therapeutics. Lastly, our affinity pull-downs and mass-spectrometry identify P. falciparum’s outer membrane proteins as likely targets for polybasic peptide medications. Since poly-lysine dendrimers are already FDA-approved for drug delivery, their adaptation as antimalarial drugs presents a promising new therapeutic strategy. One-Sentence Summary Our study demonstrates that poly-lysine peptides, particularly those modified through PEG-ylation or in the form of poly-lysine dendrimers, can effectively reduce Plasmodium falciparum, the causative agent of malaria, in human erythrocytes in vitro, with potential for use as a promising new antimalarial therapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":411517,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243052,"name":"Katherine Floyd","orcid":"0000-0001-8574-9480","position":1,"is_corresponding":false},{"id":1192239,"name":"Erath Jessey","orcid":null,"position":2,"is_corresponding":false},{"id":554829,"name":"Jenny Kim Kim","orcid":null,"position":3,"is_corresponding":false},{"id":420914,"name":"Peter O. Bayguinov","orcid":"0000-0002-5365-7490","position":4,"is_corresponding":false},{"id":420916,"name":"James A. J. Fitzpatrick","orcid":"0000-0002-7907-3602","position":5,"is_corresponding":false},{"id":1192240,"name":"Dennis Goldfrab","orcid":null,"position":6,"is_corresponding":false},{"id":1191930,"name":"Marko Jovanović","orcid":"0000-0002-8387-2271","position":7,"is_corresponding":false},{"id":610917,"name":"Abhai K. Tripathi","orcid":"0000-0001-9848-0142","position":8,"is_corresponding":false},{"id":494055,"name":"Sergej Djuranović","orcid":"0000-0002-9417-0822","position":9,"is_corresponding":false},{"id":494051,"name":"Slavica Pavlovic Djuranovic","orcid":"0000-0003-4219-0095","position":10,"is_corresponding":false},{"id":1192238,"name":"Roshan Sivakumar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:21:42.971455Z","pmid":"37745508","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}